Development of a D-FISH method to detect DEK/CAN fusion resulting from t(6;9)(p23;q34) in patients with acute myelogenous leukemia.

The t(6;9)(p23;q34)-DEK/CAN fusion occurs with an incidence of 1-5% in adult patients with acute myelogenous leukemia (AML) and tends to have an unfavorable prognosis at diagnosis. Due to the subtle appearance of this chromosome rearrangement, both initial detection and minimal residual disease (MRD) tracking by conventional karyotyping can be difficult. Unfortunately, no commercial or previously published fluorescence in situ hybridization (FISH) strategies exist for this recurrent anomaly. We have developed a highly sensitive assay using dual-color, double-fusion FISH (D-FISH), which can be used both for initial detection and MRD monitoring. We analyzed archived bone marrow samples from 15 patients with a previously identified t(6;9)(p23;q34) and 10 corresponding post-treatment samples. The results demonstrate that our D-FISH method effectively identified all abnormal samples, including a low-level MRD sample that was considered to be normal by conventional cytogenetic analysis. Normal value ranges were established from 30 negative controls to be < 0.6% when 500 interphase nuclei were analyzed. The development of this sensitive D-FISH strategy for the detection of the t(6;9)(p23;q34) adds to the AML FISH testing repertoire, and is effective in the detection of low-level disease in post-treatment samples in these patients.

Increased incidence of cervical intraepithelial neoplasia grade 3 and human papillomavirus infection at a family planning clinic.

A five-fold increase in the incidence of histologically-proven cervical intraepithelial neoplasia grade 3 (CIN3) was observed for patients attending the Christchurch family planning clinic in 1985 compared with the preceding three years. There were 51 new cases in 1985 and a yearly average of 9.3 between 1982 and 1984. There was an increase also in cervical smears showing evidence of human papillomavirus (HPV) infection. The time interval between the last normal smear and the diagnosis of CIN3 was short, averaging 2.3 years. CIN3 patients were young (average 28.9 years); they had a high average number of sexual partners (10.1). These findings support the theory of a sexually transmitted precursor to the development of CIN3. The 1985 surge in CIN3 may reflect an increased prevalence of this oncogenic agent. The aim of screening is to prevent invasive cervical carcinoma. Annual smears should therefore be considered for young sexually-active women in view of the short time interval between normal smears and the development of CIN3.